As an improved ophthalmic technique for diagnosing and monitoring glaucoma (and other diseases that cause retinal degeneration), electroretinogram (ERG) measurement appears to have considerable promise. Current research indicates that dynamic ERG response to retinal stimulation from an alternating pattern may be a significantly better and earlier indicator of retinal degeneration than conventional intraocular pressure tests, visual field tests, and cup-to-disc ratios.
The specific problem to which the invention can be applied is a pattern electroretinogram (PERG) system capable of assessing the function of the retinal ganglion cell layer and nerve fiber layer, and evaluating retinal degeneration such as for glaucoma diagnosis and management. In addition to permitting the entire retina to be evaluated, the test should have the following features: (1) Sensitivity and specificity; (2) Reproducibility; (3) Ease of use in very young, elderly and disabled patients; (4) Brevity of performance; (5) Easy interpretation; (6) Minimal requirement for patient response and/or attention; (7) Reliability in spite of ocular media opacities; and (8) Freedom from refractive correction.
Ophthalmologists have traditionally relied on relatively few clinical tests and findings to diagnose and follow patients with open angle glaucoma. Recently, the sensitivity of even the most sophisticated tests have been questioned. One recent study has shown that glaucoma suspects may lose up to fifty percent of their optic nerve fibers before developing visual loss detectable by kinetic perimetry (Reference 10, listed at the end of the Background). Moreover, in glaucoma, loss of the nerve fibers and, subsequently, the ganglion cells themselves, have been shown by histopathologic studies (References 1,8,9,11).
Newly developed automated threshold static perimetry has also failed to solve this problem because, in many cases, it is difficult to distinguish progressive visual field loss from short- and long-term fluctuations, as well as from the effects of media opacities and miosis. Additionally, these tests (a) require a significant amount of concentration and participation from patients that is sometimes difficult, (b) require administration by trained personnel, and (c) require a high degree of understanding for accurate interpretation.
Other parameters used to evaluate glaucoma, namely cup to disc (C/D) ratios and intraocular pressures, also have significant disadvantages. Even with the best tools and methods, both inter- and intra-observer variability of the C/D ratio assessment are inevitable (Reference 2). In addition, up to fifty percent of the optic nerve fibers may be lost prior to detectable visual field abnormalities. Elevated Intraocular Pressure (IOP) is well known to be far more prevalent than is open angle glaucoma as defined by visual field loss. In addition, the IOP is extremely variable even in patients with known glaucoma and, as a sole parameter for glaucoma management, is grossly inadequate (Reference 12).
Pattern ERG (PERG) has significant advantages over these current approaches to diagnosing and evaluating retinal degeneration from glaucoma. In PERG, the patient views a pattern image (such as light and dark squares shown on a CRT), and the retina is stimulated by alternating the pattern (such as by light/dark pattern reversal), generating an ERG amplitude response. Many studies have confirmed that the PERG amplitude is significantly reduced in patients with glaucoma (References 3-7,13).
PERG is particularly advantageous because research indicates that the PERG response signal is generated only by the proximal (inner) layers, which are precisely the layers selectively damaged by glaucoma. Thus, PERG has great potential for diagnosing and monitoring retinal degeneration caused by glaucoma (References 3-7,13,14).
Moreover, at least one study has shown that abnormal PERG amplitudes are manifested in patients with only ocular hypertension (i.e. glaucoma suspects) (Reference 14). This group of patients have elevated IOP, but no demonstrable visual field or C/D abnormalities. Many of these patients later go on to develop visual field or C/D abnormalities and hence are diagnosed to have glaucoma. The PERG abnormalities found in these patients suggest that PERG is a more sensitive indicator of early glaucomatous degeneration than are currently utilized tests, at least in some patients.
Conventional PERG has several important advantages: (1) Direct measurement, i.e., minimal cognitive patient response is required for generating PERG data; (2) Brevity, i.e., one pattern alternation generates a corresponding PERG response; and (3) Specificity, i.e., PERG response is generated by the ganglion cells (the retinal component damaged in glaucoma).
However, the current technique for performing PERG measurements based on viewing a CRT pattern has at least two important limitations: (1) It requires an accurate refractive correction to obtain sharp pattern contrast; and (2) It tests only a narrow field-of-view within the posterior retina.
The above-referenced field-of-view limitation, i.e., a field-of-view limited to the posterior-most regions of the retina, is particularly disadvantageous because the posterior retina survives best to the final stage of glaucoma, while the ganglion cells in the more anterior regions of the retina are frequently lost first. This phenomenon of glaucomatous damage is demonstrated by the generalized constriction seen on standard visual field testing of patients with glaucoma. This pattern of vision loss progresses until only a central island of vision remains, and it is precisely this most resistant region that is being stimulated by a standard PERG.
The entire retina can be stimulated by a flash ERG (FERG) procedure. In a standard flash ERG (FERG), a flash of light generates a dynamic ERG amplitude response caused by the stimulation of both the distal (photoreceptor) and proximal (ganglion) layers of the retina in all retinal regions (posterior, middle and anterior). This mass retinal response is of no advantage in monitoring glaucomatous retinal degeneration, which selectively affects only the nerve fibers and their parent ganglion cells.
Systems employing laser interferometers and potential acuity meters have been used to evaluate visual acuity in some subjects. However, the interferometer projects an interference pattern, while the potential acuity meter projects an eye chart. Thus, these projection systems have not been used for PERG testing, and are capable only of projecting into limited areas of the posterior retina.
Accordingly, a specific need exists for a PERG system capable of stimulating the posterior, medial, and anterior portions of the retina. A more general need exists for an ophthalmic instrument for projecting images (modulated light) onto a selected area of the retina.